Background:Inflammatory reactions are recognized as pivotal in spinal cord injury(SCI),with the antiinflammatory role of polarized microglia crucial in mitigating such injury.The present study aimed to determine the p...Background:Inflammatory reactions are recognized as pivotal in spinal cord injury(SCI),with the antiinflammatory role of polarized microglia crucial in mitigating such injury.The present study aimed to determine the protective effects of GsMTx4 on functional recovery in a mouse model of SCI and investigate the role of GsMTx4 in cytokine-induced microglial activation and associated molecular mechanisms.Methods:We assessed the effects of GsMTx4 on motor function in a mouse model of SCI,including neuronal survival and activated microglia in the vicinity of the injury after SCI.We also investigated the effects of GsMTx4 on expression of relevant inflammatory factors involved in cytokine-induced microglial activation and the associated signaling pathways.Results:GsMTx4 effectively promoted functional recovery in mice and alleviated nerve damage after SCI.Additionally,GsMTx4 facilitated the transition of microglia from the M1 phenotype to the M2 phenotype,suppressed microglial activation,and reduced the expression of corresponding inflammatory mediators.These effects may involve modulation of neurogenic inflammation through the Piezo1/NFkB/STAT6 pathway,at least in part.Conclusion:GsMTx4 safeguards against SCI by regulating microglial polarization,potentially via the Piezo1/NFkB/STAT6 pathway,offering initial evidence supporting the potential therapeutic efficacy of GsMTx4 for treatment of SCI.展开更多
Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary dis-eases.Acute lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality ...Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary dis-eases.Acute lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality because of the limitations of targeted intervention.Accordingly,in the present study,we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide(LPS)in vitro and in vivo.Then,chitosan-stabilized bovine serum albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological function.Through aerosol inhalation,NC-GsMTx4 im-proved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ALI.Mechanistically,GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 signaling.In summary,our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression,and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.展开更多
基金supported by the Program of Jiangsu Science and Technology Department(BE2022737)the Program of Suzhou Health Commission(LCZX202110,GSWS2020078,SZXK202111).
文摘Background:Inflammatory reactions are recognized as pivotal in spinal cord injury(SCI),with the antiinflammatory role of polarized microglia crucial in mitigating such injury.The present study aimed to determine the protective effects of GsMTx4 on functional recovery in a mouse model of SCI and investigate the role of GsMTx4 in cytokine-induced microglial activation and associated molecular mechanisms.Methods:We assessed the effects of GsMTx4 on motor function in a mouse model of SCI,including neuronal survival and activated microglia in the vicinity of the injury after SCI.We also investigated the effects of GsMTx4 on expression of relevant inflammatory factors involved in cytokine-induced microglial activation and the associated signaling pathways.Results:GsMTx4 effectively promoted functional recovery in mice and alleviated nerve damage after SCI.Additionally,GsMTx4 facilitated the transition of microglia from the M1 phenotype to the M2 phenotype,suppressed microglial activation,and reduced the expression of corresponding inflammatory mediators.These effects may involve modulation of neurogenic inflammation through the Piezo1/NFkB/STAT6 pathway,at least in part.Conclusion:GsMTx4 safeguards against SCI by regulating microglial polarization,potentially via the Piezo1/NFkB/STAT6 pathway,offering initial evidence supporting the potential therapeutic efficacy of GsMTx4 for treatment of SCI.
基金supported by the Science and Technology Plan of Jiangxi Provincial Health Commission(No.SKJP220201115)Live Science and Technology of Suzhou(No.SS201862)the Prior-ity Academic Program Development of Jiangsu Higher Education Institutions(PAPD).Translational Research Grant of NCRCH(No.2020WSB08).
文摘Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary dis-eases.Acute lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality because of the limitations of targeted intervention.Accordingly,in the present study,we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide(LPS)in vitro and in vivo.Then,chitosan-stabilized bovine serum albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological function.Through aerosol inhalation,NC-GsMTx4 im-proved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ALI.Mechanistically,GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 signaling.In summary,our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression,and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.
